title: Personalized prediction of EGFR mutation-induced drug resistance in lung cancer.
abstract: EGFR mutation-induced drug resistance has significantly impaired the potency of small molecule tyrosine kinase inhibitors in lung cancer treatment. Computational approaches can provide powerful and efficient techniques in the investigation of drug resistance. In our work, the EGFR mutation feature is characterized by the energy components of binding free energy (concerning the mutant-inhibitor complex), and we combine it with specific personal features for 168 clinical subjects to construct a personalized drug resistance prediction model. The 3D structure of an EGFR mutant is computationally predicted from its protein sequence, after which the dynamics of the bound mutant-inhibitor complex is simulated via AMBER and the binding free energy of the complex is calculated based on the dynamics. The utilization of extreme learning machines and leave-one-out cross-validation promises a successful identification of resistant subjects with high accuracy. Overall, our study demonstrates advantages in the development of personalized medicine/therapy design and innovative drug discovery.
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong.
authors.forename: Debby D
authors.initials: DD
authors.lastname: Wang
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.forename: Maria
authors.initials: M
authors.lastname: Wong
authors.forename: Victor
authors.initials: V
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004355:Drug Stability; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009154:Mutation; D057285:Precision Medicine; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors